Atmospheric Pressure Ionization sources, in particular Electrospray and Atmospheric Pressure Chemical Ionization sources, interfaced to mass spectrometers have become widely used for the analysis of compounds found in solutions. ES/MS system have been described in U.S. Pat. Nos. 4,531,056, 4,542,293 and 4,209,696. The technique and its applications have been reviewed by Penn et. ala, Mass Spectrometry Reviews 1990, 9, 37-70 and by Smith et. al., Mass Spectrometry Reviews 1991, 10, 359-451. Electrospray and APCI have been routinely used as ion sources for on-line LC/MS and CE/MS systems. In Electrospray ionization, as diagrammatically illustrated in FIG. 1, sample bearing liquid is introduced into an atmospheric pressure bath gas through a tube which is generally sharpened at the exit end. A 3 to 6 kilovolt relative potential is applied between the ES liquid introduction tube or needle exit and the surrounding electrodes causing Electrospraying of the sample bearing liquid to occur. Charged liquid droplets formed in the Electrospray process evaporate as they pass through a counter current bath gas in the Electrospray chamber. The charged droplet evaporation leads to Rayleigh disintegration followed by further evaporation and shrinking of droplets. This process eventually leads to the desorption of ions directly from the smaller diameter charged droplet surface into the gas phase. A portion of the atmospheric pressure bath gas, entrained ions and charged liquid droplets are swept into vacuum through an orifice or capillary annulus. When capillaries are used as the orifice into vacuum, the capillary may be heated to further aid in droplet evaporation and ion desorption from the liquid droplets. Ions exiting the capillary enter vacuum through a free jet expansion and are accelerated and focused into a mass analyzer.
Nebulization assist techniques have been applied to Electrospray to extend the range of operation while simplifying its use. High frequency ultrasonic nebulization applied at the Electrospray needle tip has been used to assist the Electrospray droplet formation process. An ultrasonic nebulization assisted electrospray apparatus is manufactured by Analytica of Branford Inc. Alternatively a pneumatic nebulization assisted electrospray has been reported first by Mack et al. J. of Chemical Physics, 1970, 62, 4977-4986 and later in U.S. Pat. No. 4,861,988. Both of These nebulization assisted electrospray techniques have been successful at simplifying operation and improving performance of Electrospray when producing positive or negative ions from liquids entering the Electrospray source with flow rates ranging from less than 1 .mu.l/min to over 2 ml/min and with a wide range of solution conductivity's and solvent compositions. Unassisted Electrospray has difficulty forming stable sprays for aqueous solutions with higher surface tension, highly conductive solutions and for liquid flow rates over 50 .mu.l/min. For some applications which require interfacing Electrospray to capillary electrophoresis or in cases where limited sample is available, lowering the liquid flow rates may be preferable. The use of unassisted electrospray may yield higher performance for these applications when compared with using nebulization assist techniques. In both assisted and unassisted electrospray methods, it is helpful to observe the spray when optimizing ES source performance. A commercial ES/MS quadrupole mass spectrometer produced by Sciex has used a window located at the end of the cylindrical ES or pneumatic nebulization assisted ES source opposite to the ES endplate or vacuum orifice end. The internal diameter of this ES source is over 7 inches in diameter and the cylindrical side wall is maintained at ground potential. The endplate of this ES source is maintained at a potential within 1000 volts of ground. The window is used to visualize the direction in which a pneumatic nebulizer assisted Electrospray, which produces coarse droplet sizes, is aimed during operation. The position of this viewing window does not allow optimal viewing of the unassisted Electrospray spray. No conductive electrode was placed inside this window to shield the ES source from the effects of space charge buildup on the inside dielectric surface of the window during operation.
The droplet sizes produced by unassisted Electrospray are a function of the liquid flow rate exiting the sharpened Electrospray liquid introduction tube tip. When conserving sample or running microbore fused silica LC columns interfaced to the ES source, the liquid flow rates are typically below 6 .mu.l/min. For a liquid flow rate of approximately 3 .mu.l/min, the charged liquid droplet size distribution produced is monodisperse with a mean diameter of 2.93 microns. The Electrospray charged droplets fan out due to space charge repulsion as they move away from the needle tip towards the counter electrode endplate. The moving droplets evaporate rapidly in the countercurrent drying gas and decrease in size as they approach the end plate. The droplet diameters produced in the low flow rate Electrospray plume are so small that forward light scattering must be used to observe the spray plume. The Electrospray droplets produced initially can be seen from Mie scattering of visible, but as the droplets evaporate they enter the Rayleigh scattering regime for visible light. A Tyndall color spectra can be observed from a white light source scattered through an Electrospray droplet plume produced from liquid flows of 1 of 2 .mu.l/min. The quality and stability of the unassisted Electrospray can be quickly ascertained by a direct observation of the spray quality. The present invention includes the incorporation of windows or view ports located in positions around the side walls of an Electrospray chamber. In particular the invention includes windows or view ports which are located on opposite sides of the ES chamber so a light source or viewing angle can be positioned to optimized observed scattering intensity from the ES spray plume. Voltages and needle position can be adjusted to visually optimize Electrospray performance during operation. If the MS signal becomes unstable or decreases, a quick visual observation of the ES plume can determine if the trouble is in the ES spray performance. For example a pulsatile liquid delivery pump or an air bubble emerging at the needle tip will temporarily interrupt the Electrospray process and the lack of spray can be visually observed. The side walls of the ES chamber are conductive to avoid space charge buildup of ions hitting the walls or windows along the side walls of the ES chamber. The conductive side wall electrode, usually cylindrical in shape and extending along most of the sidewall length of the ES chamber, is configured to allot viewing through the electrode into the ES source.
When positive ions are produced in ES sources, the ES liquid introduction tube exit tip is maintained at a positive kilovolt potential relative to the counter electrode endplate and the surrounding cylindrical electrode or lens. When the ES source configuration includes countercurrent bath gas flow, the ES chamber endplate is usually maintained between 0 to 1000 volts above the orifice or capillary entrance potential. The sidewall cylindrical shaped lens potential is usually between 0 and positive 3000 volts relative to the endplate potential in the positive ion operating mode. The direction of the relative potentials would be reversed for the Electrospray production of ions with negative potential. The potentials of the ES chamber electrodes are generally set so that charged entities which leave the ES needle tip are directed and focused by the electrostatic field toward the orifice or capillary entrance into vacuum. In one embodiment of the invention, it was found for some modes of assisted and unassisted ES operation that positive or negative ion signal level can be significantly increased by increasing the potential difference between the cylindrical electrode and the ES liquid introduction tube while maintaining a constant differential between the ES liquid introduction tube and the endplate and capillary entrance electrodes. The mechanism for this increase in sensitivity when an apparent defocusing voltage is set on the cylindrical electrode is not yet clearly understood. The increased sensitivity with increasing cylindrical electrode relative potential appears to be more pronounced at higher liquid flow rates so the defocusing may help to fan out droplets for increased drying efficiency. The increased cylindrical electrode potential relative to the ES liquid introduction needle tip potential may cause an increase in the net charge density per droplet produced resulting in an increase in ES/MS sensitivity.
The inclusion of windows in the sidewalls of an API source and configuring the source chamber to have a semitransparent sidewall electrode which allows viewing of the ES spray and the APCI corona discharge region during operation aids in and simplifies performance optimization and system troubleshooting during operation or either source type. When the side wall electrode is configured to run with a potential difference of up to thousands of volts between the ES liquid introduction needle tip, ES chamber endplate and orifice plate, higher signal intensities can be achieved in unassisted and nebulization assisted Electrospray operation. Increasing ES/MS sensitivity and the improving the convenience of API operation expands the range of applications to which API/MS analysis can be routinely applied.